Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects.
TL;DR: It is suggested that dexamethasone affects nocturnal production of melatonin by means of mechanisms within the pineal gland.
Abstract: There is no conclusive evidence supporting an interaction between the pineal gland and the hypothalamic-pituitary-adrenal axis. In this study, 11 healthy adults (six women, five men; aged 18-47 years) received a placebo the first night and 1 mg dexamethasone the next night at either 1800 or 2300 h. Administration of 1 mg of dexamethasone was followed by an attenuation of the nocturnal production of melatonin in 9 of 11 subjects. A significant reduction was found between melatonin plasma levels before and after dexamethasone at 0400 h (P less than 0.01, t test for dependent groups). It is suggested that dexamethasone affects nocturnal production of melatonin by means of mechanisms within the pineal gland.
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TL;DR: The data indicate that pineal influences have a place in the physiologic regulation of aging and evidence suggests that melatonin and/or pineal-related factors could produce their effects through an influence on thyroid function.
Abstract: Dark-cycle, night administration of the pineal hormone melatonin in drinking water to aging mice (15 months of age) prolongs survival of BALB/c females from 23.8 to 28.1 months and preserves aspects of their youthful state. Similar results were seen in New Zealand Black females beginning at 5 months and C57BL/6 males beginning at 19 months. As melatonin is produced in circadian fashion from the pineal, we grafted pineals from young 3- to 4-month-old donors into the thymus of 20-month-old syngeneic C57BL/6 male recipients, and a 12% increase in survival was induced. Prolongation of survival was also seen on pineal transplant to the thymus in C57BL/6, BALB/cJ, and hybrid female mice at 16, 19, and 22 months. In all studies, the endogenous pineal of grafted mice was left in situ. Pineal grafted aged mice display a remarkable maintenance of thymic structure and cellularity. Preservation of T-cell-mediated function, despite age, as measured by response to oxazolone is seen. Other evidence suggests that melatonin and/or pineal-related factors could produce their effects through an influence on thyroid function. These data indicate that pineal influences have a place in the physiologic regulation of aging.
269 citations
135 citations
TL;DR: The melatonin measures were not consistently related to any of the previously reported hypothalamic-pituitary-adrenal cortical axis measures in these subjects, and failed to confirm a "low melatonin syndrome" or an inverse relationship between nocturnal melatonin andnocturnal cortisol concentrations in depression.
Abstract: To ascertain the extent of dysregulation of melatonin secretion in endogenous depression, we measured nocturnal and diurnal serum melatonin concentrations in 38 depressed patients (23 women and 15 men) who had primary, definite endogenous depression according to the Research Diagnostic Criteria and in 38 individually matched normal control subjects. Previous reports have suggested that such patients may have reduced nocturnal melatonin secretion, often in conjunction with increased hypothalamic-pituitary-adrenal cortical axis activity. This has been considered as a possible reflection of reduced noradrenergic activity in depression. Compared with their matched controls, the depressed patients showed a trend toward a significantly elevated average nocturnal melatonin concentration that was accounted for primarily by the 14 premenopausal women--the postmenopausal female and male depressive patients did not differ significantly from their respective controls. The average diurnal melatonin concentration also showed a trend toward being higher in both the female and male depressed patients. The melatonin measures were not consistently related to any of the previously reported hypothalamic-pituitary-adrenal cortical axis measures in these subjects. Our findings thus failed to confirm a "low melatonin syndrome" or an inverse relationship between nocturnal melatonin and nocturnal cortisol concentrations in depression. This discrepancy may be related to methodologic differences among studies; our data are in accord with those findings of the one other reported study in which normal controls were individually matched to patients on variables that were known to influence melatonin secretion. Most of the studies, including ours, have been cross-sectional.(ABSTRACT TRUNCATED AT 250 WORDS)
121 citations
TL;DR: In this review, the evidence pointing towards an undeniable role of melatonin in certain clinical instances will be presented and discussed.
Abstract: Pineal function and its main hormonal product melatonin has often been ignored by many clinicians. In this review, the evidence pointing towards an undeniable role of melatonin in certain clinical instances will be presented and discussed. In the last 3 decades tremendous advances in the understanding of the biochemistry and physiology of the pineal gland have occurred. It is now evident that the pineal interacts with many endocrine as well as non-endocrine tissues to influence their metabolic activity. The most extensively studied pineal effect on the neuroendocrinereproductive axis is by no means the only or necessarily the most important role of this gland, which through its hormone, melatonin, is able to modulate many organs and functions.
119 citations
TL;DR: The observation of exercise-induced phase shifts of the onset of melatonin secretion is interpreted as evidence that, in humans as in rodents, increased physical activity during the habitual rest period is capable of altering circadian clock function.
Abstract: Accumulating evidence suggests that exercise may have both rapid and delayed effects on human melatonin secretion. Indeed, exercise may acutely (i.e., within minutes) alter melatonin levels and result in a shift of the onset of nocturnal melatonin 12 to 24 h later. The presence and nature of both acute and delayed effects appear to be dependent on the timing of exercise. The presence of a detectable acute effect also depends on the duration, intensity, and type of exercise. Late evening exercise during the rising phase of melatonin secretion may blunt melatonin levels. High-intensity exercise during the nighttime period, when melatonin levels already are elevated, consistently results in a further (nearly 50%) elevation of melatonin levels. No effect of low-intensity exercise performed at the same circadian phase could be detected. Irrespective of intensity, exercise near the offset of melatonin secretion or during the daytime has no consistent acute effect on melatonin secretion. Nighttime exercise, whether of moderate or high intensity, results in phase delays of the melatonin onset on the next evening. In support of the concept that a shift of the melatonin onset on the day after nighttime exercise represents a shift of intrinsic circadian timing is the observation that similar phase shifts (in both direction and magnitude) may be observed simultaneously for the onset of the circadian elevation of thyrotropin secretion. The observation of exercise-induced phase shifts of the onset of melatonin secretion is, therefore, interpreted as evidence that, in humans as in rodents, increased physical activity during the habitual rest period is capable of altering circadian clock function.
111 citations
Cites result from "Influence of dexamethasone on noctu..."
...This hypothesis was consistent with evidence that dexamethasone, a synthetic glucocorticoid, reduces plasma melatonin levels in humans (Demisch et al., 1988) and that inhibition of cortisol by metyrapone increases urinary melatonin excretion (Brismar et al....
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TL;DR: Treatment with reserpine, a compound that depletes norepinephrine from nerves, 1-propranolol, a beta-adrenergic blocking agent, or cycloheximide, an inhibitor of protein synthesis, abolishes the nocturnal increase in serotonin N-acetyltransferase activity, indicating that the enzyme activity is modulated by neural release of nore Pinephrine from sympathetic nerves via beta- adrenergic receptors.
Abstract: Serotonin N-acetyltransferase (EC 2.3.1.5) activity in the rat pineal organ is enhanced 50-fold at night. Rats exposed to light at night or kept in darkness during the daytime do not show any elevation of enzyme activity. Treatment with reserpine, a compound that depletes norepinephrine from nerves, 1-propranolol, a β-adrenergic blocking agent, or cycloheximide, an inhibitor of protein synthesis, abolishes the nocturnal increase in serotonin N-acetyltransferase activity, indicating that the enzyme activity is modulated by neural release of norepinephrine from sympathetic nerves via β-adrenergic receptors, and that the increase in enzyme activity is due to synthesis of new enzyme molecules. When rats are exposed to light at night or injected with 1-propranolol, there is a precipitous fall in serotonin N-acetyltransferase activity (half-life 5 min). Cycloheximide administered at night results in a slow fall in enzyme activity (half-life 60 min). When rats are kept in darkness and then exposed to light for 10 min, L-isoproterenol rapidly initiates the elevation of serotonin N-acetyltransferase activity to the initial level in 60 min. On the other hand, when the rats are kept in continuous light, L-isoproterenol initiates an increase in serotonin N-acetyltransferase activity after a lag phase of 60 min. The results indicate that there are two types of changes in serotonin N-acetyltransferase activity; a rapid increase and decrease mediated by the β-adrenergic receptor, and a slow increase and decrease in enzyme activity that appears to represent the turnover of the enzyme.
279 citations
TL;DR: The hypothesis that pituitary ACTH regulation is altered in depressed patients with abnormal DSTs is supported and melatonin is proposed to be an inhibiting factor for CRF during depression.
145 citations
TL;DR: It is reported that adrenal corticoids can alter the sensitivity of this system to NA, and this system has provided the basis for a revised catecholamine hypothesis of affective disorders.
Abstract: Considerable evidence indicates that alterations in the availability of noradrenaline (NA) at postsynaptic sites can cause compensatory changes in the NA stimulated cyclic AMP generating system in various brain regions. Thus, an increased responsiveness to NA has been reported in the limbic forebrain and cortex following reserpine or 6-hydroxydopamine1–3. Conversely, manipulations which increase the availability of NA at receptor sites (monoamine oxidase (MAO) inhibitors, electroconvulsive treatment (ECT), tricyclic antidepressants) cause a decrease in responsiveness4–6. This up and down-regulation of central noradrenergic sensitivity is generally linked to changes of the density of β-adrenergic receptors7–10. The findings that psychotropic drugs which can either precipitate (reserpine) or alleviate (tricyclic antidepressants, MAO inhibitors and also ECT) depressive states cause opposite changes in the NA receptor-coupled adenylate cyclase system in brain have provided the basis for a revised catecholamine hypothesis of affective disorders11. It has also been suggested that the pituitary adrenal axis may have a role in mood disorders12. Since manipulation of the levels of corticosterone through bilateral adrenalectomy can alter the sensitivity of catecholamine-sensitive adenylate cyclase systems in preparations from liver13,14 and adipose tissue15, we have tried to determine if corticosterone could regulate the NA receptor-coupled adenylate cyclase system in brain tissue. We now report that adrenal corticoids can alter the sensitivity of this system to NA.
109 citations
TL;DR: New protein synthesis is always required for N-acetyltransferase induction; however, the requirement for RNA synthesis is variable, and contributes to the length of the lag period for induction.
Abstract: The lag period in the induction of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase EC 2.3.1.5) by catecholamines via the beta-adrenergic receptor varies with the length of exposure of the rat to light or darkness. If rats have been exposed to light and reduced sympathetic nerve activity for more than 12 hr, this lag period is 1-2 hr long. Under these conditions, actinomycin D completely blocks the induction of N-acetyltransferase by isoproterenol and by dibutyryl adenosine 3':5'-cyclic monophosphate (cyclic AMP). In contrast, if enzyme activity is caused to fall by brief exposure to light at night when N-acetyltransferase activity is high, reinduction by catecholamines occurs almost immediately. In this case, actinomycin D does not block the reinduction of N-acetyltransferase by isoproterenol or by dibutyryl cyclic AMP. Cycloheximide blocks N-acetyltransferase induction under all conditions tested. Thus, new protein synthesis is always required for N-acetyltransferase induction; however, the requirement for RNA synthesis is variable, and contributes to the length of the lag period for induction. It is postulated that both beta-adrenergic stimulation and dibutyryl cyclic AMP act intracellularly at two separate sites in the induction of pineal N-acetyltransferase. One site is in the stimulation of transcription, and the other is in the stimulation of post-transcriptional events.
84 citations
TL;DR: It appears that the density of beta 1-receptors in the caudate is normally affected by changing levels of endogenous catecholamines, similar to that of other beta-adrenergic receptors that receive endogenous input.
34 citations